The Role And Mechanism Of Hydrogen Sulfide In Acute Hyperoxaluria Nephropathy

Objective:To investigate the mechanism of hydrogen sulfide(H2S)in inhibiting acute hyperoxaluria nephropathy in mice.Methods:Twenty-five C57BL/6 mice(male)were randomly divided into five groups:(1)control group:normal saline(2)modeling group:3%sodium oxalate water was fed,and sodium oxalate solution was injected intraperitoneal at 100mg/kg on the fourth day;(3)1?mol/kg.dNaHS treatment group:3%sodium oxalate water was fed,and sodium oxalate solution was injected intraperitoneal at 100mg/kg on the fourth day,with NaHS solution at 1?mol/kg.d daily;(4)10?mol/kg.dNaHS treatment group:3%sodium oxalate water was fed,and sodium oxalate solution was injected intraperitoneal at 100mg/kg on the fourth day,with NaHS solution at 10?mol/kg.d daily;(5)30?mol/kg.dNaHStreatment group:3%sodium oxalate water was fed,and sodium oxalate solution was injected intraperitoneal at 100mg/kg on the fourth day,with NaHS solution at 1?mol/kg.d daily.On the fifth day,the mice were sacrificed and plasma and kidney were stored.The right kidney was stored in formalin solution at room temperature for HE staining.Wersten Blot and RT-PCR detected the expression of ASC.Wersten Blot measured the expression of H2S synthesis-related enzymes CBS and CSE,inflammasome-related proteins caspase-1 and p-p42/44,and apoptosis-related proteins Bax,caspase-3 and bcl-2.The expression of IL-1?and IL-18 weretested by Elisa.Results:HE staining prompted thatcompared with the control group,the renal tissue structure of the mice in the modeling group was disorganized,with severe renal tubular damage,inflammatory cell infiltration and fibrosis in the renal interstitium,and the tubule interstitial score was significantly increased(P<0.001).The tubule interstitial scoredistinct decreased with NaHS treatment(P<0.001).Compared with the control group,the expressions of ASC,caspase-1 and P-p42/44,Bax and caspase-3 in the real tissue were significantly increased in the modeling group.Serum levels of IL-1?and IL-18 were also increased in the model group.The expressions of CBS,CSE and Bcl-2 were significantly decreased in the modeling group.After treatment with 1-10?mol/kg.dNaHS solution,the expressions of the above inflammasome regulating proteins and factors and apoptotic regulating proteins decreased,while the expressions of CBS and CSE and apoptotic regulating proteinBcl-2 were up-regulated,with statistically significant differences.Conclusion:1.Exogenous H2S can improve the renal function of acute hyperoxaluria nephropathy mice.2.H2S can improve the renal function of acute acute hyperoxaluria nephropathy mice by inhibiting inflammasome andapoptotic regulating protein.